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Background: Generalized myasthenia gravis (gMG) is a potentially life threatening chronic autoimmune disease that can impair patients’ ability to work effectively and increase reliance on public support benefits. A public economic framework was used to explore how treatment influences patients’ and caregivers’ economic activity, including tax revenues and public support in Canada. Methods: Natural history of gMG was simulated using a multi-state Markov cohort model. Health states were based on MG Activities of Daily Living (MG-ADL) total score in patients with AChR-Ab+ refractory gMG. Treatment, costs, and economic outcomes of patients taking efgartigimod were compared with alternative therapeutic options. Canadian public support benefits were based on official government sources. Results: Improved MG-ADL states predict higher workforce participation, lower rates of disability and less caregiving needs, resulting in higher tax revenues and less public support costs. Compared to alternative therapeutic options, efgartigimod is estimated to yield lifetime fiscal gains of $458,755 that exceed the incremental cost of $291,073, suggesting the Canadian government receives $1.6 for every $1.0 spent on efgartigimod for the treatment of gMG. Conclusions: Compared with alternative options, efgartigimod generated a positive fiscal return for the Canadian governments with additional savings from disease management, public benefits, and averted tax revenue losses.
The First Large Absorption Survey in H i (FLASH) is a large-area radio survey for neutral hydrogen in and around galaxies in the intermediate redshift range $0.4\lt z\lt1.0$, using the 21-cm H i absorption line as a probe of cold neutral gas. The survey uses the ASKAP radio telescope and will cover 24,000 deg$^2$ of sky over the next five years. FLASH breaks new ground in two ways – it is the first large H i absorption survey to be carried out without any optical preselection of targets, and we use an automated Bayesian line-finding tool to search through large datasets and assign a statistical significance to potential line detections. Two Pilot Surveys, covering around 3000 deg$^2$ of sky, were carried out in 2019-22 to test and verify the strategy for the full FLASH survey. The processed data products from these Pilot Surveys (spectral-line cubes, continuum images, and catalogues) are public and available online. In this paper, we describe the FLASH spectral-line and continuum data products and discuss the quality of the H i spectra and the completeness of our automated line search. Finally, we present a set of 30 new H i absorption lines that were robustly detected in the Pilot Surveys, almost doubling the number of known H i absorption systems at $0.4\lt z\lt1$. The detected lines span a wide range in H i optical depth, including three lines with a peak optical depth $\tau\gt1$, and appear to be a mixture of intervening and associated systems. Interestingly, around two-thirds of the lines found in this untargeted sample are detected against sources with a peaked-spectrum radio continuum, which are only a minor (5–20%) fraction of the overall radio-source population. The detection rate for H i absorption lines in the Pilot Surveys (0.3 to 0.5 lines per 40 deg$^2$ ASKAP field) is a factor of two below the expected value. One possible reason for this is the presence of a range of spectral-line artefacts in the Pilot Survey data that have now been mitigated and are not expected to recur in the full FLASH survey. A future paper in this series will discuss the host galaxies of the H i absorption systems identified here.
Objectives/Goals: The timing of neurosurgery is highly variable for post-hemorrhagic hydrocephalus (PHH) of prematurity. We sought to utilize microvascular imaging (MVI) in ultrasound (US) to identify biomarkers to discern the opportune time for intervention and to analyze the cerebrospinal fluid (CSF) characteristics as they pertain to neurosurgical outcome. Methods/Study Population: The inclusion criteria for the study are admission to the neonatal intensive care unit (NICU) with a diagnosis of Papile grade III or IV. Exclusion criteria are congenital hydrocephalus and hydrocephalus secondary to myelomeningocele/brain tumor/vascular malformation. We are a level IV tertiary referral center. Our current clinical care pathway utilizes brain US at admission and at weekly intervals. Patients who meet certain clinical and radiographic parameters undergo temporary or permanent CSF diversion. Results/Anticipated Results: NEL was implemented at our institution for PHH of prematurity in fall 2022. To date, we have had 20 patients who were diagnosed with grade III or IV IVH, of which 12 qualified for NEL. Our preliminary safety and feasibility results as well as the innovative bedside technique pioneered at our institution are currently in revision stages for publication. Preliminary results of the MVI data have yielded that hyperemia may confer venous congestion in the germinal matrix, which should then alert the neurosurgeon to delay any intervention to avoid progression of intraventricular blood. With regard to CSF characteristics, we anticipate that protein, cell count, hemoglobin, iron, and ferritin will decrease with NEL. Discussion/Significance of Impact: The timing of PHH of prematurity is highly variable. We expect that MVI will offer radiographic biomarkers to guide optimal timing of neurosurgical intervention. A better understanding of CSF characteristics could potentially educate the neurosurgeon with regard to optimal timing of permanent CSF diversion based on specific CSF parameters.
We present the first results from a new backend on the Australian Square Kilometre Array Pathfinder, the Commensal Realtime ASKAP Fast Transient COherent (CRACO) upgrade. CRACO records millisecond time resolution visibility data, and searches for dispersed fast transient signals including fast radio bursts (FRB), pulsars, and ultra-long period objects (ULPO). With the visibility data, CRACO can localise the transient events to arcsecond-level precision after the detection. Here, we describe the CRACO system and report the result from a sky survey carried out by CRACO at 110-ms resolution during its commissioning phase. During the survey, CRACO detected two FRBs (including one discovered solely with CRACO, FRB 20231027A), reported more precise localisations for four pulsars, discovered two new RRATs, and detected one known ULPO, GPM J1839 $-$10, through its sub-pulse structure. We present a sensitivity calibration of CRACO, finding that it achieves the expected sensitivity of 11.6 Jy ms to bursts of 110 ms duration or less. CRACO is currently running at a 13.8 ms time resolution and aims at a 1.7 ms time resolution before the end of 2024. The planned CRACO has an expected sensitivity of 1.5 Jy ms to bursts of 1.7 ms duration or less and can detect $10\times$ more FRBs than the current CRAFT incoherent sum system (i.e. 0.5 $-$2 localised FRBs per day), enabling us to better constrain the models for FRBs and use them as cosmological probes.
During the past 30 yr an impasse has developed in the discovery and commercialization of synthetic herbicides with new molecular targets and novel chemistries. Similarly, there has been little success with bioherbicides, both microbial and chemical. These bioherbicides are needed to combat fast-growing herbicide resistance and to fulfill the need for more environmentally and toxicologically safe herbicides. In response to this substantial and growing opportunity, numerous start-up companies are utilizing novel approaches to provide new tools for weed management. These diverse new tools broaden the scope of discovery, encompassing advanced computational, bioinformatic, and imaging platforms; plant genome–editing and targeted protein degradation technologies; and machine learning and artificial intelligence (AI)-based strategies. This review contains summaries of the presentations of 10 such companies that took part in a symposium held at the WSSA annual meeting in 2024. Four of the companies are developing microbial bioherbicides or natural product–based herbicides, and the other six are using advanced technologies, such as AI, to accelerate the discovery of herbicides with novel molecular target sites or to develop non-GMO, herbicide-resistant crops.
Passive oxygenation with non-rebreather face mask (NRFM) has been used during cardiac arrest as an alternative to positive pressure ventilation (PPV) with bag-valve-mask (BVM) to minimize chest compression disruptions. A dual-channel pharyngeal oxygen delivery device (PODD) was created to open obstructed upper airways and provide oxygen at the glottic opening. It was hypothesized for this study that the PODD can deliver oxygen as efficiently as BVM or NRFM and oropharyngeal airway (OPA) in a cardiopulmonary resuscitation (CPR) manikin model.
Methods:
Oxygen concentration was measured in test lungs within a resuscitation manikin. These lungs were modified to mimic physiologic volumes, expansion, collapse, and recoil. Automated compressions were administered. Five trials were performed for each of five arms: (1) CPR with 30:2 compression-to-ventilation ratio using BVM with 15 liters per minute (LPM) oxygen; continuous compressions with passive oxygenation using (2) NRFM and OPA with 15 LPM oxygen, (3) PODD with 10 LPM oxygen, (4) PODD with 15 LPM oxygen; and (5) control arm with compressions only.
Results:
Mean peak oxygen concentrations were: (1) 30:2 CPR with BVM 49.3% (SD = 2.6%); (2) NRFM 47.7% (SD = 0.2%); (3) PODD with 10 LPM oxygen 52.3% (SD = 0.4%); (4) PODD with 15 LPM oxygen 62.7% (SD = 0.3%); and (5) control 21% (SD = 0%). Oxygen concentrations rose rapidly and remained steady with passive oxygenation, unlike 30:2 CPR with BVM, which rose after each ventilation and decreased until the next ventilation cycle (sawtooth pattern, mean concentration 40% [SD = 3%]).
Conclusions:
Continuous compressions and passive oxygenation with the PODD resulted in higher lung oxygen concentrations than NRFM and BVM while minimizing CPR interruptions in a manikin model.
Background: Reducing oral corticosteroids (OCS) use can alleviate the risk of many adverse events related to long-term OCS use. Here, we evaluate real-world utilization of OCS among patients with generalized myasthenia gravis (gMG) over the first 6 months following efgartigimod initiation. Methods: Patients with gMG using OCS who initiated efgartigimod treatment were identified retrospectively from an open US medical and pharmacy claims database (IQVIA Longitudinal Access and Adjudication Data [LAAD], April 2016-April 2023). Average daily dose (ADD) of OCS was analyzed during the 3-month period preceding efgartigimod initiation, and at 3 and 6 months post-efgartigimod initiation. Results: Of 231 patients assessed, 17 (7.4%), 109 (47.1%), and 105 (45.5%) had baseline OCS ADD of 0–5 mg, 5–20 mg, or >20 mg, respectively. At 3 and 6 months post-efgartigimod, 82 (35%) and 99 (43%) patients, respectively, reduced ADD by ≥5 mg. Proportion of patients with ADD of 0–5 mg increased >3-fold (7% baseline vs. 26% 6 months post-efgartigimod) and proportion of patients with ADD of >20 mg decreased by 35% (45% baseline vs. 29% 6 months post-efgartigimod) following efgartigimod initiation. Conclusions: Approximately 43% of patients were able to decrease steroid use or achieved steroid-free status within 6 months of efgartigimod treatment initiation.
Radiocarbon (14C) dating of sediment deposition around Antarctica is often challenging due to heterogeneity in sources and ages of organic carbon in the sediment. Chemical and thermochemical techniques have been used to separate organic carbon when microfossils are not present. These techniques generally improve on bulk sediment dates, but they necessitate assumptions about the age spectra of specific molecules or compound classes and about the chemical heterogeneity of thermochemical separations. To address this, the Rafter Radiocarbon Laboratory has established parallel ramped pyrolysis oxidation (RPO) and ramped pyrolysis-gas chromatography-mass spectrometry (Py-GC-MS) systems to thermochemically separate distinct carbon fractions, diagnose the chemical composition of each fraction, and target suitable RPO fractions for radiocarbon dating. Three case studies of sediment taken from locations around Antarctica are presented to demonstrate the implementation of combined RPO-AMS and Py-GC-MS to provide more robust age determination in detrital sediment stratigraphy. These three depositional environments are good examples of analytical and interpretive challenges related to oceanographic conditions, carbon sources, and other factors. Using parallel RPO-AMS and Py-GC-MS analyses, we reduce the number of radiocarbon measurements required, minimize run times, provide context for unexpected 14C ages, and better support interpretations of radiocarbon measurements in the context of environmental reconstruction.
The COVID-19 pandemic disrupted many areas of life, including culturally accepted practices at end-of-life care, funeral rites, and access to social, community, and professional support. This survey investigated the mental health outcomes of Australians bereaved during this time to determine how these factors might have impacted bereavement outcomes.
Methods
An online survey indexing pandemic and bereavement experiences, levels of grief, depression, anxiety, and health, work, and social impairment. Latent class analysis (LCA) was used to identify groups of individuals who shared similar symptom patterns. Multinomial regressions identified pandemic-related, loss-related, and sociodemographic correlates of class membership.
Results
1911 Australian adults completed the survey. The LCA identified four classes: low symptoms (46.8%), grief (17.3%), depression/anxiety (17.7%), and grief/depression/anxiety (18.2%). The latter group reported the highest levels of health, work, and social impairment. The death of a child or partner and an inability to care for the deceased due to COVID-19 public health measures were correlated with grief symptoms (with or without depression and anxiety). Preparedness for the person's death and levels of pandemic-related loneliness and social isolation differentiated all four classes. Unemployment was associated with depression/anxiety (with or without grief).
Conclusions
COVID-19 had profound impacts for the way we lived and died, with effects that are likely to ricochet through society into the foreseeable future. These lessons learned must inform policymakers and healthcare professionals to improve bereavement care and ensure preparedness during and following future predicted pandemics to prevent negative impacts.
Obtaining complete and accurate information in recruitment registries is essential for matching potential participants to research studies for which they qualify. Since electronic health record (EHR) systems are required to make patient data available to external systems, an interface between EHRs and recruitment registries may improve accuracy and completeness of volunteers’ profiles. We tested this hypothesis on ResearchMatch (RM), a disease- and institution-neutral recruitment registry with 1357 studies across 255 institutions.
Methods:
We developed an interface where volunteers signing up for RM can authorize transfer of demographic data, medical conditions, and medications from the EHR into a registration form. We obtained feedback from a panel of community members to determine acceptability of the planned integration. We then developed the EHR interface and performed an evaluation study of 100 patients to determine whether RM profiles generated with EHR-assisted adjudication included more conditions and medications than those without the EHR connection.
Results:
Community member feedback revealed that members of the public were willing to authenticate into the EHR from RM with proper messaging about choice and privacy. The evaluation study showed that out of 100 participants, 75 included more conditions and 69 included more medications in RM profiles completed with the EHR connection than those without. Participants also completed the EHR-connected profiles in 16 fewer seconds than non-EHR-connected profiles.
Conclusions:
The EHR to RM integration could lead to more complete profiles, less participant burden, and better study matches for many of the over 148,000 volunteers who participate in ResearchMatch.
The spatial distribution of in situ sessile organisms, including those from the fossil record, provides information about life histories, such as possible dispersal and/or settlement mechanisms, and how taxa interact with one another and their local environments. At Nilpena Ediacara National Park (NENP), South Australia, the exquisite preservation and excavation of 33 fossiliferous bedding planes from the Ediacara Member of the Rawnsley Quartzite reveals in situ communities of the Ediacara Biota. Here, the spatial distributions of three relatively common taxa, Tribrachidium, Rugoconites, and Obamus, occurring on excavated surfaces were analyzed using spatial point pattern analysis. Tribrachidium have a variable spatial distribution, implying that settlement or post-settlement conditions/preferences had an effect on populations. Rugoconites display aggregation, possibly related to their reproductive methods in combination with settlement location availability at the time of dispersal and/or settlement. Additionally, post-settlement environmental controls could have affected Rugoconites on other surfaces, resulting in lower populations and densities. Both Tribrachidium and Rugoconites also commonly occur as individuals or in low numbers on a number of beds, thus constraining possible reproductive strategies and environmental/substrate preferences. The distribution of Obamus is consistent with selective settlement, aggregating near conspecifics and on substrates of mature microbial mat. This dispersal process is the first example of substrate-selective dispersal among the Ediacara Biota, thus making Obamus similar to numerous modern sessile invertebrates with similar dispersal and settlement strategies.
Despite evidence for its efficacy, exposure therapy for anxiety is rarely used in routine care settings. Efforts to address one major barrier to its use – therapists’ negative beliefs about exposure – have included therapist-level implementation strategies, such as training and consultation. Experiential training, in which therapists themselves undergo exposures, has recently demonstrated feasibility, acceptability and preliminary effectiveness for increasing exposure use.
Aims:
This study aimed to assess: (1) therapists’ perceptions of experiential training and (2) barriers and facilitators to implementing exposure following training.
Method:
Therapists who underwent experiential training (n=12) completed qualitative interviews and quantitative questionnaires. Interviews were coded using an integrated approach, combining both inductive and deductive approaches. Mixed methods analyses examined how themes varied by practice setting (community mental health versus private practice) and exposure use.
Results:
Results highlight how therapist-level factors, such as clinician self-efficacy, interact with inner- and outer-setting factors. Participants reported positive perceptions of exposure after training; they noted that directly addressing myths about exposure and experiencing exposures themselves improved their attitudes toward exposure. Consistent with prior literature, issues such as insufficient supervisory support, organizational constraints, and client characteristics made it challenging to implement exposures.
Discussion:
Results highlight the benefits of experiential training, while also highlighting the need to consider contextual determinants. Differences in responses across practice settings highlight areas for intervention and the importance of tailoring implementation strategies. Barriers that were specific to therapists who did not use exposure (e.g. hesitancy about its appropriateness for most clients) point to directions for future implementation efforts.
A survey of attitudes towards the welfare and rights of animals was conducted in universities in 11 European and Asian countries, to improve understanding of cultural differences that might impact on trade and international relations. Collaborators’ universities were recruited in each country to assist in the design, translation and administration of the survey via the internet in a convenient selection of the country's universities, providing 3,433 student responses from at least 103 universities. Respondents rated the acceptability of 43 major concerns about animals (focused on type of use, animal integrity, killing animals, animal welfare, experimentation on animals, changes in animal genotypes, the environment for animals and societal attitudes towards animals). Students from European countries had more concern for animal welfare than students from Asian countries, which may be partly explained by increased affluence of European students as there was a positive correlation between student expenditure and concern for animal welfare and rights. Southern and central European countries had most concern for animal rights and unnatural practices. Those in communist or former communist countries in Asia and Europe had most concern about killing animals and those in northern European countries the least. Regional similarities between neighbouring countries were evident in responses to animal issues and there were no differences between ethnic groups within a country. Thus, there were national and continental differences in European and Asian students’ attitudes to animals’ welfare and rights, which appear to arise as a result of the socio-political situation in regions rather than religious or other differences.
Horseshoe crabs as a group are renowned for their morphological conservatism punctuated by marked shifts in morphology associated with the occupation of non-marine environments and have been suggested to exhibit a consistent developmental trajectory throughout their evolutionary history. Here, we report a new species of horseshoe crab from the Ordovician (Late Sandbian) of Kingston, Ontario, Canada, from juvenile and adult material. This new species provides critical insight into the ontogeny and morphology of the earliest horseshoe crabs, indicating that at least some Palaeozoic forms had freely articulating tergites anterior to the fused thoracetron and an opisthosoma comprising 13 segments.
We present the most sensitive and detailed view of the neutral hydrogen (${\rm H\small I}$) emission associated with the Small Magellanic Cloud (SMC), through the combination of data from the Australian Square Kilometre Array Pathfinder (ASKAP) and Parkes (Murriyang), as part of the Galactic Australian Square Kilometre Array Pathfinder (GASKAP) pilot survey. These GASKAP-HI pilot observations, for the first time, reveal ${\rm H\small I}$ in the SMC on similar physical scales as other important tracers of the interstellar medium, such as molecular gas and dust. The resultant image cube possesses an rms noise level of 1.1 K ($1.6\,\mathrm{mJy\ beam}^{-1}$) $\mathrm{per}\ 0.98\,\mathrm{km\ s}^{-1}$ spectral channel with an angular resolution of $30^{\prime\prime}$ (${\sim}10\,\mathrm{pc}$). We discuss the calibration scheme and the custom imaging pipeline that utilises a joint deconvolution approach, efficiently distributed across a computing cluster, to accurately recover the emission extending across the entire ${\sim}25\,\mathrm{deg}^2$ field-of-view. We provide an overview of the data products and characterise several aspects including the noise properties as a function of angular resolution and the represented spatial scales by deriving the global transfer function over the full spectral range. A preliminary spatial power spectrum analysis on individual spectral channels reveals that the power law nature of the density distribution extends down to scales of 10 pc. We highlight the scientific potential of these data by comparing the properties of an outflowing high-velocity cloud with previous ASKAP+Parkes ${\rm H\small I}$ test observations.
Subjective tinnitus is a common symptom, and there is often an underlying otological cause. This study investigated the degree of tinnitus-related annoyance in patients with chronic otitis media and analysed whether associations with tinnitus severity exist.
Method
The multinational collaborative Chronic Otitis Media Questionnaire-12 study collected prospective data on 478 adult patients suffering from chronic otitis media across 9 otology referral centres in 8 countries. Based on this dataset, we investigated tinnitus severity using participant responses to item 7 of a native version of the Chronic Otitis Media Questionnaire-12.
Results
With respect to tinnitus severity, 23.8 per cent, 17.4 per cent, 15.5 per cent, and 43.4 per cent of participants reported no, minor, moderate, and major inconvenience or greater, respectively. The absence of ear discharge, absence of cholesteatoma, and poorer disease-specific health-related quality-of-life were associated with increased tinnitus severity in patients with chronic otitis media, whereas age, hearing disability and geographical region showed no association.
Conclusion
This analysis provided novel insight into potential risk factors for tinnitus in patients with chronic otitis media.
The Variables and Slow Transients Survey (VAST) on the Australian Square Kilometre Array Pathfinder (ASKAP) is designed to detect highly variable and transient radio sources on timescales from 5 s to $\sim\!5$ yr. In this paper, we present the survey description, observation strategy and initial results from the VAST Phase I Pilot Survey. This pilot survey consists of $\sim\!162$ h of observations conducted at a central frequency of 888 MHz between 2019 August and 2020 August, with a typical rms sensitivity of $0.24\ \mathrm{mJy\ beam}^{-1}$ and angular resolution of $12-20$ arcseconds. There are 113 fields, each of which was observed for 12 min integration time, with between 5 and 13 repeats, with cadences between 1 day and 8 months. The total area of the pilot survey footprint is 5 131 square degrees, covering six distinct regions of the sky. An initial search of two of these regions, totalling 1 646 square degrees, revealed 28 highly variable and/or transient sources. Seven of these are known pulsars, including the millisecond pulsar J2039–5617. Another seven are stars, four of which have no previously reported radio detection (SCR J0533–4257, LEHPM 2-783, UCAC3 89–412162 and 2MASS J22414436–6119311). Of the remaining 14 sources, two are active galactic nuclei, six are associated with galaxies and the other six have no multi-wavelength counterparts and are yet to be identified.
In this paper, we describe the system design and capabilities of the Australian Square Kilometre Array Pathfinder (ASKAP) radio telescope at the conclusion of its construction project and commencement of science operations. ASKAP is one of the first radio telescopes to deploy phased array feed (PAF) technology on a large scale, giving it an instantaneous field of view that covers $31\,\textrm{deg}^{2}$ at $800\,\textrm{MHz}$. As a two-dimensional array of 36$\times$12 m antennas, with baselines ranging from 22 m to 6 km, ASKAP also has excellent snapshot imaging capability and 10 arcsec resolution. This, combined with 288 MHz of instantaneous bandwidth and a unique third axis of rotation on each antenna, gives ASKAP the capability to create high dynamic range images of large sky areas very quickly. It is an excellent telescope for surveys between 700 and $1800\,\textrm{MHz}$ and is expected to facilitate great advances in our understanding of galaxy formation, cosmology, and radio transients while opening new parameter space for discovery of the unknown.
The Rapid ASKAP Continuum Survey (RACS) is the first large-area survey to be conducted with the full 36-antenna Australian Square Kilometre Array Pathfinder (ASKAP) telescope. RACS will provide a shallow model of the ASKAP sky that will aid the calibration of future deep ASKAP surveys. RACS will cover the whole sky visible from the ASKAP site in Western Australia and will cover the full ASKAP band of 700–1800 MHz. The RACS images are generally deeper than the existing NRAO VLA Sky Survey and Sydney University Molonglo Sky Survey radio surveys and have better spatial resolution. All RACS survey products will be public, including radio images (with $\sim$ 15 arcsec resolution) and catalogues of about three million source components with spectral index and polarisation information. In this paper, we present a description of the RACS survey and the first data release of 903 images covering the sky south of declination $+41^\circ$ made over a 288-MHz band centred at 887.5 MHz.
A progressive decrement in muscle mass and muscle function, sarcopoenia, accompanies ageing. The loss of skeletal muscle mass and function is the main feature of sarcopoenia. Preventing the loss of muscle mass is relevant since sarcopoenia can have a significant impact on mobility and the quality of life of older people. Dietary protein and physical activity have an essential role in slowing muscle mass loss and helping to maintain muscle function. However, the current recommendations for daily protein ingestion for older persons appear to be too low and are in need of adjustment. In this review, we discuss the skeletal muscle response to protein ingestion, and review the data examining current dietary protein recommendations in the older subjects. Furthermore, we review the concept of protein quality and the important role that nutrient-dense protein (NDP) sources play in meeting overall nutrient requirements and improving dietary quality. Overall, the current evidence endorses an increase in the daily ingestion of protein with emphasis on the ingestion of NDP choices by older adults.